id: Q99816 gene_symbol: TSG101 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- TSG101 encodes the UEV-domain ESCRT-I subunit that binds ubiquitin/PTAP-type motifs and scaffolds ESCRT-I with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits. Its conserved core role is ESCRT-I-mediated sorting of ubiquitinated endocytic cargo into multivesicular bodies and reverse-topology membrane fission. TSG101 also participates in ESCRT-I-dependent phagophore/autophagosome closure, best represented biologically as autophagosome assembly rather than generic macroautophagy. Viral budding, cytokinesis, exosome release, and transcription/cell-growth annotations are supported non-core or over-broad branches. alternative_products: - name: '1' id: Q99816-1 - name: '2' id: Q99816-2 sequence_note: VSP_004440 existing_annotations: - term: id: GO:0000813 label: ESCRT I complex evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation. action: ACCEPT reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits. additional_reference_ids: &id001 - PMID:11595185 - PMID:12900395 - PMID:31519728 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: &id002 - &id006 reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Component of the ESCRT-I complex - &id007 reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Binds to ubiquitinated cargo proteins - &id008 reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: required for the sorting of endocytic ubiquitinated cargos into - &id009 reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: which consists of TSG101, VPS28, a VPS37 protein - &id010 reference_id: PMID:12900395 supporting_text: ESCRT-I subunit Tsg101 - &id011 reference_id: PMID:12900395 supporting_text: the initial recruitment of ESCRT-I to endosomes - term: id: GO:0008333 label: endosome to lysosome transport evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: endosome to lysosome transport is supported as part of the core ESCRT-I endosomal cargo-sorting role. action: ACCEPT reason: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports endosome-to-lysosome/vacuolar delivery of cargo. additional_reference_ids: - PMID:11595185 - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: &id004 - &id025 reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: required for the sorting of endocytic ubiquitinated cargos into - &id026 reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: multivesicular bodies - &id027 reference_id: PMID:12900395 supporting_text: indirectly regulates multivesicular body formation - &id028 reference_id: PMID:12900395 supporting_text: the initial recruitment of ESCRT-I to endosomes - term: id: GO:0000813 label: ESCRT I complex evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: part_of review: summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation. action: ACCEPT reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits. additional_reference_ids: *id001 supported_by: *id002 - term: id: GO:0005634 label: nucleus evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: nucleus localization is supported but is not the core proteostasis annotation. action: KEEP_AS_NON_CORE reason: These locations reflect broad cytosolic/nuclear/midbody/plasma-membrane contexts for TSG101 and ESCRT-associated functions, but the core review focus is ESCRT-I endosomal sorting and phagophore closure. additional_reference_ids: &id003 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Mainly cytoplasmic - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Nuclear localization is cell cycle-dependent - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: localization to the midbody during cytokinesis - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: cytoplasm localization is supported but is not the core proteostasis annotation. action: KEEP_AS_NON_CORE reason: These locations reflect broad cytosolic/nuclear/midbody/plasma-membrane contexts for TSG101 and ESCRT-associated functions, but the core review focus is ESCRT-I endosomal sorting and phagophore closure. additional_reference_ids: *id003 supported_by: - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Mainly cytoplasmic - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Nuclear localization is cell cycle-dependent - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: localization to the midbody during cytokinesis - term: id: GO:0005813 label: centrosome evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: centrosome localization is supported but is not the core proteostasis annotation. action: KEEP_AS_NON_CORE reason: These locations reflect broad cytosolic/nuclear/midbody/plasma-membrane contexts for TSG101 and ESCRT-associated functions, but the core review focus is ESCRT-I endosomal sorting and phagophore closure. additional_reference_ids: *id003 supported_by: - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Mainly cytoplasmic - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Nuclear localization is cell cycle-dependent - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: localization to the midbody during cytokinesis - term: id: GO:0006355 label: regulation of DNA-templated transcription evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: regulation of DNA-templated transcription is a legacy/non-core nuclear transcription annotation and likely overstates the current functional picture. action: MARK_AS_OVER_ANNOTATED reason: The synthesized evidence supports ESCRT-I ubiquitin/cargo sorting and membrane scission; DNA/transcription terms are not central and are not well integrated with the current proteostasis review. additional_reference_ids: *id003 supported_by: - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: May be involved in cell growth and differentiation - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Acts as a negative growth regulator - term: id: GO:0015031 label: protein transport evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in review: summary: Generic protein transport is true but should be replaced by MVB/endosome-to-lysosome cargo sorting terms. action: MODIFY reason: The specific TSG101 transport role is ESCRT-I sorting of ubiquitinated cargo through MVB/endolysosomal pathways, not undifferentiated protein transport. additional_reference_ids: *id001 supported_by: *id004 proposed_replacement_terms: - id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway - id: GO:0036258 label: multivesicular body assembly - term: id: GO:0016236 label: macroautophagy evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: macroautophagy is too broad or late-fusion-biased for the TSG101 autophagy role. action: MODIFY reason: The best-supported PN autophagy interpretation is ESCRT-I-mediated phagophore/autophagosome closure, which is better represented by autophagosome assembly. additional_reference_ids: &id018 - PMID:31519728 - PMID:31010855 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: &id019 - &id029 reference_id: PMID:31519728 supporting_text: VPS37A directs ESCRT recruitment for phagophore closure - &id030 reference_id: PMID:31519728 supporting_text: the core ESCRT-I components TSG101 and VPS28 - &id031 reference_id: PMID:31519728 supporting_text: required for autophagosome completion - &id032 reference_id: PMID:31519728 supporting_text: phagophore closure in mammalian cells - &id033 reference_id: PMID:31010855 supporting_text: mediates AP sealing - &id034 reference_id: PMID:31010855 supporting_text: ESCRT catalyzes AP closure proposed_replacement_terms: &id020 - id: GO:0000045 label: autophagosome assembly - term: id: GO:0031901 label: early endosome membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: early endosome membrane localization is supported and relevant to ESCRT-I cargo sorting. action: ACCEPT reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions. additional_reference_ids: - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: &id005 - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Early endosome membrane - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Late endosome membrane - reference_id: PMID:12900395 supporting_text: Tsg101 to late endosomes - reference_id: PMID:12900395 supporting_text: colocalize on a subpopulation of endosomes - term: id: GO:0031902 label: late endosome membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: late endosome membrane localization is supported and relevant to ESCRT-I cargo sorting. action: ACCEPT reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions. additional_reference_ids: - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id005 - term: id: GO:0036258 label: multivesicular body assembly evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: multivesicular body assembly is supported as part of the core ESCRT-I endosomal cargo-sorting role. action: ACCEPT reason: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports endosome-to-lysosome/vacuolar delivery of cargo. additional_reference_ids: - PMID:11595185 - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id004 - term: id: GO:0039702 label: viral budding via host ESCRT complex evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: viral budding via host ESCRT complex is supported but reflects host-pathogen exploitation of ESCRT-I. action: KEEP_AS_NON_CORE reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review. additional_reference_ids: &id015 - PMID:11595185 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: &id016 - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Involved in the budding of many viruses - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: interaction is essential for viral particle budding - reference_id: PMID:11595185 supporting_text: required for HIV-1 budding - reference_id: PMID:11595185 supporting_text: arrests HIV-1 budding at a late stage - term: id: GO:0045892 label: negative regulation of DNA-templated transcription evidence_type: IEA original_reference_id: GO_REF:0000108 qualifier: involved_in review: summary: negative regulation of DNA-templated transcription is a legacy/non-core nuclear transcription annotation and likely overstates the current functional picture. action: MARK_AS_OVER_ANNOTATED reason: The synthesized evidence supports ESCRT-I ubiquitin/cargo sorting and membrane scission; DNA/transcription terms are not central and are not well integrated with the current proteostasis review. additional_reference_ids: *id003 supported_by: - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: May be involved in cell growth and differentiation - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Acts as a negative growth regulator - term: id: GO:0090543 label: Flemming body evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Flemming body localization is supported but is not the core proteostasis annotation. action: KEEP_AS_NON_CORE reason: These locations reflect broad cytosolic/nuclear/midbody/plasma-membrane contexts for TSG101 and ESCRT-associated functions, but the core review focus is ESCRT-I endosomal sorting and phagophore closure. additional_reference_ids: *id003 supported_by: - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Mainly cytoplasmic - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Nuclear localization is cell cycle-dependent - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: localization to the midbody during cytokinesis - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:12802020 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - &id012 reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Binds to ubiquitinated cargo proteins - &id013 reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Interacts with ubiquitin proposed_replacement_terms: &id014 - id: GO:0043130 label: ubiquitin binding - id: GO:0000813 label: ESCRT I complex - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:12900395 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:15033475 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:15611048 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16118794 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16189514 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17174262 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17350572 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17853893 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19060904 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19549727 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20176808 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:26871637 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:27107012 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:28514442 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:31515488 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:33961781 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:35044719 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:35271311 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:37100772 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:37219487 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:39526800 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:40205054 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0003714 label: transcription corepressor activity evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: transcription corepressor activity is a legacy/non-core nuclear transcription annotation and likely overstates the current functional picture. action: MARK_AS_OVER_ANNOTATED reason: The synthesized evidence supports ESCRT-I ubiquitin/cargo sorting and membrane scission; DNA/transcription terms are not central and are not well integrated with the current proteostasis review. additional_reference_ids: *id003 supported_by: - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: May be involved in cell growth and differentiation - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Acts as a negative growth regulator - term: id: GO:0046755 label: viral budding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: viral budding is supported but reflects host-pathogen exploitation of ESCRT-I. action: KEEP_AS_NON_CORE reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review. additional_reference_ids: *id015 supported_by: *id016 - term: id: GO:0070062 label: extracellular exosome evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: Extracellular exosome detection is supported but is a non-core localization/context. action: KEEP_AS_NON_CORE reason: TSG101 is commonly detected in exosome preparations and regulates exosomal release, but this is secondary to its ESCRT-I membrane-remodeling role. additional_reference_ids: *id003 supported_by: &id017 - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Required for the exosomal release of SDCBP, CD63 and syndecan - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: extracellular release of microvesicles - term: id: GO:1990182 label: exosomal secretion evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: exosomal secretion is supported but non-core in this PN review. action: KEEP_AS_NON_CORE reason: TSG101 contributes to exosome/microvesicle release, but the proteostasis core here is ESCRT-I endosomal cargo sorting and autophagophore closure. additional_reference_ids: *id003 supported_by: *id017 - term: id: GO:2000397 label: positive regulation of ubiquitin-dependent endocytosis evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: positive regulation of ubiquitin-dependent endocytosis is supported as a cargo-sorting consequence of ESCRT-I function. action: ACCEPT reason: TSG101-mediated ESCRT-I sorting of ubiquitinated receptors into the MVB/lysosomal pathway explains EGFR/endocytosis down-regulation annotations. additional_reference_ids: - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id004 - term: id: GO:0005829 label: cytosol evidence_type: IDA original_reference_id: GO_REF:0000052 qualifier: located_in review: summary: cytosol localization is supported but is not the core proteostasis annotation. action: KEEP_AS_NON_CORE reason: These locations reflect broad cytosolic/nuclear/midbody/plasma-membrane contexts for TSG101 and ESCRT-associated functions, but the core review focus is ESCRT-I endosomal sorting and phagophore closure. additional_reference_ids: *id003 supported_by: - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Mainly cytoplasmic - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Nuclear localization is cell cycle-dependent - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: localization to the midbody during cytokinesis - term: id: GO:0005634 label: nucleus evidence_type: EXP original_reference_id: PMID:17229889 qualifier: located_in review: summary: nucleus localization is supported but is not the core proteostasis annotation. action: KEEP_AS_NON_CORE reason: These locations reflect broad cytosolic/nuclear/midbody/plasma-membrane contexts for TSG101 and ESCRT-associated functions, but the core review focus is ESCRT-I endosomal sorting and phagophore closure. additional_reference_ids: *id003 supported_by: - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Mainly cytoplasmic - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Nuclear localization is cell cycle-dependent - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: localization to the midbody during cytokinesis - term: id: GO:0005737 label: cytoplasm evidence_type: EXP original_reference_id: PMID:17853893 qualifier: located_in review: summary: cytoplasm localization is supported but is not the core proteostasis annotation. action: KEEP_AS_NON_CORE reason: These locations reflect broad cytosolic/nuclear/midbody/plasma-membrane contexts for TSG101 and ESCRT-associated functions, but the core review focus is ESCRT-I endosomal sorting and phagophore closure. additional_reference_ids: *id003 supported_by: - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Mainly cytoplasmic - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Nuclear localization is cell cycle-dependent - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: localization to the midbody during cytokinesis - term: id: GO:0031901 label: early endosome membrane evidence_type: EXP original_reference_id: PMID:23166352 qualifier: located_in review: summary: early endosome membrane localization is supported and relevant to ESCRT-I cargo sorting. action: ACCEPT reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions. additional_reference_ids: - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id005 - term: id: GO:0031902 label: late endosome membrane evidence_type: EXP original_reference_id: PMID:11916981 qualifier: located_in review: summary: late endosome membrane localization is supported and relevant to ESCRT-I cargo sorting. action: ACCEPT reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions. additional_reference_ids: - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id005 - term: id: GO:0031902 label: late endosome membrane evidence_type: EXP original_reference_id: PMID:17229889 qualifier: located_in review: summary: late endosome membrane localization is supported and relevant to ESCRT-I cargo sorting. action: ACCEPT reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions. additional_reference_ids: - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id005 - term: id: GO:0061631 label: ubiquitin conjugating enzyme activity evidence_type: IKR original_reference_id: PMID:9241264 qualifier: enables negated: true review: summary: The negated ubiquitin-conjugating-enzyme annotation is correct for TSG101. action: ACCEPT reason: This is a NOT annotation. TSG101 is a UEV-domain protein that binds ubiquitin/PTAP motifs but should not be curated as an active catalytic ubiquitin-conjugating enzyme. additional_reference_ids: - PMID:9241264 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: The UEV domain binds ubiquitin - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: P-[ST]-A-P peptide motif independently - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Belongs to the ubiquitin-conjugating enzyme family. UEV - term: id: GO:0000813 label: ESCRT I complex evidence_type: IPI original_reference_id: PMID:18005716 qualifier: part_of review: summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation. action: ACCEPT reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits. additional_reference_ids: *id001 supported_by: *id002 - term: id: GO:0000813 label: ESCRT I complex evidence_type: IPI original_reference_id: PMID:21757351 qualifier: part_of review: summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation. action: ACCEPT reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits. additional_reference_ids: *id001 supported_by: *id002 - term: id: GO:0000813 label: ESCRT I complex evidence_type: IPI original_reference_id: PMID:32424346 qualifier: part_of review: summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation. action: ACCEPT reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits. additional_reference_ids: *id001 supported_by: *id002 - term: id: GO:0010008 label: endosome membrane evidence_type: NAS original_reference_id: PMID:32424346 qualifier: located_in review: summary: endosome membrane localization is supported and relevant to ESCRT-I cargo sorting. action: ACCEPT reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions. additional_reference_ids: - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id005 - term: id: GO:0036258 label: multivesicular body assembly evidence_type: NAS original_reference_id: PMID:32424346 qualifier: involved_in review: summary: multivesicular body assembly is supported as part of the core ESCRT-I endosomal cargo-sorting role. action: ACCEPT reason: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports endosome-to-lysosome/vacuolar delivery of cargo. additional_reference_ids: - PMID:11595185 - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id004 - term: id: GO:0043328 label: protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway evidence_type: NAS original_reference_id: PMID:32424346 qualifier: involved_in review: summary: protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as part of the core ESCRT-I endosomal cargo-sorting role. action: ACCEPT reason: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports endosome-to-lysosome/vacuolar delivery of cargo. additional_reference_ids: - PMID:11595185 - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id004 - term: id: GO:0090148 label: membrane fission evidence_type: NAS original_reference_id: PMID:32424346 qualifier: involved_in review: summary: Membrane fission is supported as the shared ESCRT reverse-topology membrane-remodeling activity. action: ACCEPT reason: ESCRT-I participates upstream of ESCRT-III/VPS4-driven neck scission in MVB formation, cytokinesis/viral budding, and phagophore closure contexts. additional_reference_ids: - PMID:20588296 - PMID:31519728 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: - reference_id: PMID:20588296 supporting_text: ESCRT-I and ESCRT-II direct membrane budding away from the cytosol - reference_id: PMID:31519728 supporting_text: ESCRT-mediated membrane scission in phagophore closure - reference_id: PMID:31519728 supporting_text: the core ESCRT-I components TSG101 and VPS28 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:15218037 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:1903774 label: positive regulation of viral budding via host ESCRT complex evidence_type: IMP original_reference_id: PMID:11595185 qualifier: involved_in review: summary: positive regulation of viral budding via host ESCRT complex is supported but reflects host-pathogen exploitation of ESCRT-I. action: KEEP_AS_NON_CORE reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review. additional_reference_ids: *id015 supported_by: *id016 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18005716 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0046755 label: viral budding evidence_type: IMP original_reference_id: PMID:18005716 qualifier: involved_in review: summary: viral budding is supported but reflects host-pathogen exploitation of ESCRT-I. action: KEEP_AS_NON_CORE reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review. additional_reference_ids: *id015 supported_by: *id016 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22315426 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0006858 label: extracellular transport evidence_type: IMP original_reference_id: PMID:22315426 qualifier: involved_in review: summary: extracellular transport is supported but non-core in this PN review. action: KEEP_AS_NON_CORE reason: TSG101 contributes to exosome/microvesicle release, but the proteostasis core here is ESCRT-I endosomal cargo sorting and autophagophore closure. additional_reference_ids: *id003 supported_by: *id017 - term: id: GO:0007175 label: negative regulation of epidermal growth factor-activated receptor activity evidence_type: IMP original_reference_id: PMID:16973552 qualifier: involved_in review: summary: negative regulation of epidermal growth factor-activated receptor activity is supported as a cargo-sorting consequence of ESCRT-I function. action: ACCEPT reason: TSG101-mediated ESCRT-I sorting of ubiquitinated receptors into the MVB/lysosomal pathway explains EGFR/endocytosis down-regulation annotations. additional_reference_ids: - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id004 - term: id: GO:0044877 label: protein-containing complex binding evidence_type: IDA original_reference_id: PMID:16973552 qualifier: enables review: summary: protein-containing complex binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18641129 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0016236 label: macroautophagy evidence_type: TAS original_reference_id: PMID:20588296 qualifier: involved_in review: summary: macroautophagy is too broad or late-fusion-biased for the TSG101 autophagy role. action: MODIFY reason: The best-supported PN autophagy interpretation is ESCRT-I-mediated phagophore/autophagosome closure, which is better represented by autophagosome assembly. additional_reference_ids: *id018 supported_by: *id019 proposed_replacement_terms: *id020 - term: id: GO:0042059 label: negative regulation of epidermal growth factor receptor signaling pathway evidence_type: IMP original_reference_id: PMID:16554368 qualifier: involved_in review: summary: negative regulation of epidermal growth factor receptor signaling pathway is supported as a cargo-sorting consequence of ESCRT-I function. action: ACCEPT reason: TSG101-mediated ESCRT-I sorting of ubiquitinated receptors into the MVB/lysosomal pathway explains EGFR/endocytosis down-regulation annotations. additional_reference_ids: - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id004 - term: id: GO:0000813 label: ESCRT I complex evidence_type: TAS original_reference_id: PMID:20588296 qualifier: part_of review: summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation. action: ACCEPT reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits. additional_reference_ids: *id001 supported_by: *id002 - term: id: GO:0036258 label: multivesicular body assembly evidence_type: TAS original_reference_id: PMID:20588296 qualifier: involved_in review: summary: multivesicular body assembly is supported as part of the core ESCRT-I endosomal cargo-sorting role. action: ACCEPT reason: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports endosome-to-lysosome/vacuolar delivery of cargo. additional_reference_ids: - PMID:11595185 - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id004 - term: id: GO:0039702 label: viral budding via host ESCRT complex evidence_type: TAS original_reference_id: PMID:20588296 qualifier: involved_in review: summary: viral budding via host ESCRT complex is supported but reflects host-pathogen exploitation of ESCRT-I. action: KEEP_AS_NON_CORE reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review. additional_reference_ids: *id015 supported_by: *id016 - term: id: GO:0000813 label: ESCRT I complex evidence_type: TAS original_reference_id: PMID:21118109 qualifier: part_of review: summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation. action: ACCEPT reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits. additional_reference_ids: *id001 supported_by: *id002 - term: id: GO:0097352 label: autophagosome maturation evidence_type: TAS original_reference_id: PMID:21118109 qualifier: involved_in review: summary: autophagosome maturation is too broad or late-fusion-biased for the TSG101 autophagy role. action: MODIFY reason: The best-supported PN autophagy interpretation is ESCRT-I-mediated phagophore/autophagosome closure, which is better represented by autophagosome assembly. additional_reference_ids: *id018 supported_by: *id019 proposed_replacement_terms: *id020 - term: id: GO:0043405 label: regulation of MAP kinase activity evidence_type: IMP original_reference_id: PMID:17714434 qualifier: involved_in review: summary: MAP kinase regulation is a downstream receptor-signaling consequence and not core. action: KEEP_AS_NON_CORE reason: This likely reflects altered EGFR trafficking/signaling downstream of ESCRT function rather than a direct TSG101 molecular role. additional_reference_ids: - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id004 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16973552 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0019076 label: viral release from host cell evidence_type: IMP original_reference_id: PMID:11595185 qualifier: involved_in review: summary: viral release from host cell is supported but reflects host-pathogen exploitation of ESCRT-I. action: KEEP_AS_NON_CORE reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review. additional_reference_ids: *id015 supported_by: *id016 - term: id: GO:0043130 label: ubiquitin binding evidence_type: IDA original_reference_id: PMID:11595185 qualifier: enables review: summary: Ubiquitin binding is a core TSG101 UEV-domain molecular function. action: ACCEPT reason: TSG101 binds ubiquitin/ubiquitinated cargo through its UEV domain and uses that activity in ESCRT-I cargo sorting and PTAP-motif recruitment contexts. additional_reference_ids: - PMID:11595185 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: &id021 - *id012 - *id013 - &id022 reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: The UEV domain binds ubiquitin - &id023 reference_id: PMID:11595185 supporting_text: UEV domain of Tsg101 binds - &id024 reference_id: PMID:11595185 supporting_text: to ubiquitin - term: id: GO:0046790 label: virion binding evidence_type: IDA original_reference_id: PMID:11595185 qualifier: enables review: summary: virion binding is supported but reflects host-pathogen exploitation of ESCRT-I. action: KEEP_AS_NON_CORE reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review. additional_reference_ids: *id015 supported_by: *id016 - term: id: GO:0000813 label: ESCRT I complex evidence_type: IDA original_reference_id: PMID:18005716 qualifier: part_of review: summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation. action: ACCEPT reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits. additional_reference_ids: *id001 supported_by: *id002 - term: id: GO:0005768 label: endosome evidence_type: IDA original_reference_id: PMID:17940959 qualifier: located_in review: summary: endosome localization is supported and relevant to ESCRT-I cargo sorting. action: ACCEPT reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions. additional_reference_ids: - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id005 - term: id: GO:0005886 label: plasma membrane evidence_type: IDA original_reference_id: PMID:17940959 qualifier: located_in review: summary: plasma membrane localization is supported but is not the core proteostasis annotation. action: KEEP_AS_NON_CORE reason: These locations reflect broad cytosolic/nuclear/midbody/plasma-membrane contexts for TSG101 and ESCRT-associated functions, but the core review focus is ESCRT-I endosomal sorting and phagophore closure. additional_reference_ids: *id003 supported_by: - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Mainly cytoplasmic - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Nuclear localization is cell cycle-dependent - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: localization to the midbody during cytokinesis - term: id: GO:1903774 label: positive regulation of viral budding via host ESCRT complex evidence_type: IMP original_reference_id: PMID:15218037 qualifier: involved_in review: summary: positive regulation of viral budding via host ESCRT complex is supported but reflects host-pathogen exploitation of ESCRT-I. action: KEEP_AS_NON_CORE reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review. additional_reference_ids: *id015 supported_by: *id016 - term: id: GO:0019076 label: viral release from host cell evidence_type: IMP original_reference_id: PMID:15218037 qualifier: involved_in review: summary: viral release from host cell is supported but reflects host-pathogen exploitation of ESCRT-I. action: KEEP_AS_NON_CORE reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review. additional_reference_ids: *id015 supported_by: *id016 - term: id: GO:0005769 label: early endosome evidence_type: IDA original_reference_id: PMID:11916981 qualifier: located_in review: summary: early endosome localization is supported and relevant to ESCRT-I cargo sorting. action: ACCEPT reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions. additional_reference_ids: - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id005 - term: id: GO:0043130 label: ubiquitin binding evidence_type: IDA original_reference_id: PMID:11916981 qualifier: enables review: summary: Ubiquitin binding is a core TSG101 UEV-domain molecular function. action: ACCEPT reason: TSG101 binds ubiquitin/ubiquitinated cargo through its UEV domain and uses that activity in ESCRT-I cargo sorting and PTAP-motif recruitment contexts. additional_reference_ids: - PMID:11595185 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id021 - term: id: GO:1903551 label: regulation of extracellular exosome assembly evidence_type: IMP original_reference_id: PMID:24105262 qualifier: involved_in review: summary: regulation of extracellular exosome assembly is supported but non-core in this PN review. action: KEEP_AS_NON_CORE reason: TSG101 contributes to exosome/microvesicle release, but the proteostasis core here is ESCRT-I endosomal cargo sorting and autophagophore closure. additional_reference_ids: *id003 supported_by: *id017 - term: id: GO:1903543 label: positive regulation of exosomal secretion evidence_type: IMP original_reference_id: PMID:22660413 qualifier: involved_in review: summary: positive regulation of exosomal secretion is supported but non-core in this PN review. action: KEEP_AS_NON_CORE reason: TSG101 contributes to exosome/microvesicle release, but the proteostasis core here is ESCRT-I endosomal cargo sorting and autophagophore closure. additional_reference_ids: *id003 supported_by: *id017 - term: id: GO:1903543 label: positive regulation of exosomal secretion evidence_type: IMP original_reference_id: PMID:24105262 qualifier: involved_in review: summary: positive regulation of exosomal secretion is supported but non-core in this PN review. action: KEEP_AS_NON_CORE reason: TSG101 contributes to exosome/microvesicle release, but the proteostasis core here is ESCRT-I endosomal cargo sorting and autophagophore closure. additional_reference_ids: *id003 supported_by: *id017 - term: id: GO:0070062 label: extracellular exosome evidence_type: IDA original_reference_id: PMID:23092844 qualifier: located_in review: summary: Extracellular exosome detection is supported but is a non-core localization/context. action: KEEP_AS_NON_CORE reason: TSG101 is commonly detected in exosome preparations and regulates exosomal release, but this is secondary to its ESCRT-I membrane-remodeling role. additional_reference_ids: *id003 supported_by: *id017 - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:23533145 qualifier: located_in review: summary: Extracellular exosome detection is supported but is a non-core localization/context. action: KEEP_AS_NON_CORE reason: TSG101 is commonly detected in exosome preparations and regulates exosomal release, but this is secondary to its ESCRT-I membrane-remodeling role. additional_reference_ids: *id003 supported_by: *id017 - term: id: GO:0070062 label: extracellular exosome evidence_type: IDA original_reference_id: PMID:16501490 qualifier: located_in review: summary: Extracellular exosome detection is supported but is a non-core localization/context. action: KEEP_AS_NON_CORE reason: TSG101 is commonly detected in exosome preparations and regulates exosomal release, but this is secondary to its ESCRT-I membrane-remodeling role. additional_reference_ids: *id003 supported_by: *id017 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:14519844 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0042803 label: protein homodimerization activity evidence_type: IPI original_reference_id: PMID:14519844 qualifier: enables review: summary: Homodimerization is supported as a structural interaction but is not the core functional annotation. action: KEEP_AS_NON_CORE reason: Retain this as a non-core interaction property; ESCRT-I complex membership and ubiquitin binding capture the main TSG101 role. additional_reference_ids: *id003 supported_by: - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Self-associates - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:14505570 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0000813 label: ESCRT I complex evidence_type: IDA original_reference_id: PMID:20654576 qualifier: part_of review: summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation. action: ACCEPT reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits. additional_reference_ids: *id001 supported_by: *id002 - term: id: GO:0000813 label: ESCRT I complex evidence_type: IDA original_reference_id: PMID:22232651 qualifier: part_of review: summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation. action: ACCEPT reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits. additional_reference_ids: *id001 supported_by: *id002 - term: id: GO:0043130 label: ubiquitin binding evidence_type: IDA original_reference_id: PMID:20654576 qualifier: enables review: summary: Ubiquitin binding is a core TSG101 UEV-domain molecular function. action: ACCEPT reason: TSG101 binds ubiquitin/ubiquitinated cargo through its UEV domain and uses that activity in ESCRT-I cargo sorting and PTAP-motif recruitment contexts. additional_reference_ids: - PMID:11595185 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id021 - term: id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway evidence_type: IC original_reference_id: PMID:20654576 qualifier: involved_in review: summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as part of the core ESCRT-I endosomal cargo-sorting role. action: ACCEPT reason: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports endosome-to-lysosome/vacuolar delivery of cargo. additional_reference_ids: - PMID:11595185 - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id004 - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:19056867 qualifier: located_in review: summary: Extracellular exosome detection is supported but is a non-core localization/context. action: KEEP_AS_NON_CORE reason: TSG101 is commonly detected in exosome preparations and regulates exosomal release, but this is secondary to its ESCRT-I membrane-remodeling role. additional_reference_ids: *id003 supported_by: *id017 - term: id: GO:0010008 label: endosome membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-184269 qualifier: located_in review: summary: endosome membrane localization is supported and relevant to ESCRT-I cargo sorting. action: ACCEPT reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions. additional_reference_ids: - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id005 - term: id: GO:0010008 label: endosome membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-3149434 qualifier: located_in review: summary: endosome membrane localization is supported and relevant to ESCRT-I cargo sorting. action: ACCEPT reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions. additional_reference_ids: - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id005 - term: id: GO:0010008 label: endosome membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-3159232 qualifier: located_in review: summary: endosome membrane localization is supported and relevant to ESCRT-I cargo sorting. action: ACCEPT reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions. additional_reference_ids: - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id005 - term: id: GO:0010008 label: endosome membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-917696 qualifier: located_in review: summary: endosome membrane localization is supported and relevant to ESCRT-I cargo sorting. action: ACCEPT reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions. additional_reference_ids: - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id005 - term: id: GO:0010008 label: endosome membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-917730 qualifier: located_in review: summary: endosome membrane localization is supported and relevant to ESCRT-I cargo sorting. action: ACCEPT reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions. additional_reference_ids: - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id005 - term: id: GO:0070062 label: extracellular exosome evidence_type: IDA original_reference_id: PMID:15326289 qualifier: located_in review: summary: Extracellular exosome detection is supported but is a non-core localization/context. action: KEEP_AS_NON_CORE reason: TSG101 is commonly detected in exosome preparations and regulates exosomal release, but this is secondary to its ESCRT-I membrane-remodeling role. additional_reference_ids: *id003 supported_by: *id017 - term: id: GO:0000813 label: ESCRT I complex evidence_type: IDA original_reference_id: PMID:21757351 qualifier: part_of review: summary: ESCRT-I complex membership is the central TSG101 cellular-component annotation. action: ACCEPT reason: TSG101 is a stoichiometric core ESCRT-I subunit with VPS28, VPS37-family subunits, and MVB12/UBAP-family subunits. additional_reference_ids: *id001 supported_by: *id002 - term: id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway evidence_type: IMP original_reference_id: PMID:21757351 qualifier: involved_in review: summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as part of the core ESCRT-I endosomal cargo-sorting role. action: ACCEPT reason: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports endosome-to-lysosome/vacuolar delivery of cargo. additional_reference_ids: - PMID:11595185 - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id004 - term: id: GO:0031625 label: ubiquitin protein ligase binding evidence_type: IPI original_reference_id: PMID:17229889 qualifier: enables review: summary: Ubiquitin ligase binding is supported as regulatory context but not core. action: KEEP_AS_NON_CORE reason: TSG101 interacts with LRSAM1/MGRN1 and can be monoubiquitinated, but this regulatory binding is secondary to ESCRT-I cargo sorting. additional_reference_ids: *id003 supported_by: - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Interacts with LRSAM1 - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Interacts with MGRN1 - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Monoubiquitinated at multiple sites by LRSAM1 and by MGRN1 - term: id: GO:0005769 label: early endosome evidence_type: IDA original_reference_id: PMID:17229889 qualifier: located_in review: summary: early endosome localization is supported and relevant to ESCRT-I cargo sorting. action: ACCEPT reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions. additional_reference_ids: - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id005 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18256029 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0048306 label: calcium-dependent protein binding evidence_type: IPI original_reference_id: PMID:19520058 qualifier: enables review: summary: calcium-dependent protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18077552 qualifier: enables review: summary: protein binding is too generic to represent TSG101 function. action: MARK_AS_OVER_ANNOTATED reason: The interaction evidence should be represented by ubiquitin binding, ESCRT-I complex membership, MVB sorting, viral budding context, or cytokinesis context rather than generic binding terms. additional_reference_ids: *id001 supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 proposed_replacement_terms: *id014 - term: id: GO:0005737 label: cytoplasm evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: cytoplasm localization is supported but is not the core proteostasis annotation. action: KEEP_AS_NON_CORE reason: These locations reflect broad cytosolic/nuclear/midbody/plasma-membrane contexts for TSG101 and ESCRT-associated functions, but the core review focus is ESCRT-I endosomal sorting and phagophore closure. additional_reference_ids: *id003 supported_by: - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Mainly cytoplasmic - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Nuclear localization is cell cycle-dependent - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: localization to the midbody during cytokinesis - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: PMID:18077552 qualifier: located_in review: summary: cytoplasm localization is supported but is not the core proteostasis annotation. action: KEEP_AS_NON_CORE reason: These locations reflect broad cytosolic/nuclear/midbody/plasma-membrane contexts for TSG101 and ESCRT-associated functions, but the core review focus is ESCRT-I endosomal sorting and phagophore closure. additional_reference_ids: *id003 supported_by: - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Mainly cytoplasmic - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Nuclear localization is cell cycle-dependent - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: localization to the midbody during cytokinesis - term: id: GO:0046755 label: viral budding evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: viral budding is supported but reflects host-pathogen exploitation of ESCRT-I. action: KEEP_AS_NON_CORE reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review. additional_reference_ids: *id015 supported_by: *id016 - term: id: GO:0005770 label: late endosome evidence_type: IMP original_reference_id: PMID:15126635 qualifier: located_in review: summary: late endosome localization is supported and relevant to ESCRT-I cargo sorting. action: ACCEPT reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions. additional_reference_ids: - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id005 - term: id: GO:0046755 label: viral budding evidence_type: IMP original_reference_id: PMID:15126635 qualifier: involved_in review: summary: viral budding is supported but reflects host-pathogen exploitation of ESCRT-I. action: KEEP_AS_NON_CORE reason: Viral budding/release annotations are well supported for TSG101 but are non-core for the human proteostasis-network review. additional_reference_ids: *id015 supported_by: *id016 - term: id: GO:0005771 label: multivesicular body evidence_type: TAS original_reference_id: PMID:15611048 qualifier: located_in review: summary: multivesicular body localization is supported and relevant to ESCRT-I cargo sorting. action: ACCEPT reason: TSG101 cycles between cytosol and active endosomal membranes, including early/late endosome and MVB contexts where ESCRT-I functions. additional_reference_ids: - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id005 - term: id: GO:0043130 label: ubiquitin binding evidence_type: TAS original_reference_id: PMID:15611048 qualifier: enables review: summary: Ubiquitin binding is a core TSG101 UEV-domain molecular function. action: ACCEPT reason: TSG101 binds ubiquitin/ubiquitinated cargo through its UEV domain and uses that activity in ESCRT-I cargo sorting and PTAP-motif recruitment contexts. additional_reference_ids: - PMID:11595185 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id021 - term: id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway evidence_type: IDA original_reference_id: PMID:15611048 qualifier: involved_in review: summary: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway is supported as part of the core ESCRT-I endosomal cargo-sorting role. action: ACCEPT reason: TSG101/ESCRT-I sorts ubiquitinated endocytic cargo into MVBs and thereby supports endosome-to-lysosome/vacuolar delivery of cargo. additional_reference_ids: - PMID:11595185 - PMID:12900395 - file:human/TSG101/TSG101-uniprot.txt - file:human/TSG101/TSG101-notes.md supported_by: *id004 - term: id: GO:0003677 label: DNA binding evidence_type: TAS original_reference_id: PMID:10888872 qualifier: enables review: summary: DNA binding is a legacy/non-core nuclear transcription annotation and likely overstates the current functional picture. action: MARK_AS_OVER_ANNOTATED reason: The synthesized evidence supports ESCRT-I ubiquitin/cargo sorting and membrane scission; DNA/transcription terms are not central and are not well integrated with the current proteostasis review. additional_reference_ids: *id003 supported_by: - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: May be involved in cell growth and differentiation - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Acts as a negative growth regulator - term: id: GO:0003714 label: transcription corepressor activity evidence_type: TAS original_reference_id: PMID:10888872 qualifier: enables review: summary: transcription corepressor activity is a legacy/non-core nuclear transcription annotation and likely overstates the current functional picture. action: MARK_AS_OVER_ANNOTATED reason: The synthesized evidence supports ESCRT-I ubiquitin/cargo sorting and membrane scission; DNA/transcription terms are not central and are not well integrated with the current proteostasis review. additional_reference_ids: *id003 supported_by: - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: May be involved in cell growth and differentiation - reference_id: file:human/TSG101/TSG101-uniprot.txt supporting_text: Acts as a negative growth regulator - term: id: GO:0000045 label: autophagosome assembly evidence_type: IMP original_reference_id: PMID:31519728 qualifier: involved_in review: summary: TSG101 should be added to autophagosome assembly for the ESCRT-I phagophore-closure role. action: NEW reason: The PN leaf is autophagophore sealing, and mammalian evidence shows core ESCRT-I components including TSG101 are required for autophagosome completion/phagophore closure. additional_reference_ids: *id018 supported_by: *id019 references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000024 title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: GO_REF:0000052 title: Gene Ontology annotation based on curation of immunofluorescence data findings: [] - id: GO_REF:0000107 title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara findings: [] - id: GO_REF:0000108 title: Automatic assignment of GO terms using logical inference, based on on inter-ontology links findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:10888872 title: DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. findings: [] - id: PMID:11595185 title: Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. findings: [] - id: PMID:11916981 title: Mammalian class E vps proteins recognize ubiquitin and act in the removal of endosomal protein-ubiquitin conjugates. findings: [] - id: PMID:12802020 title: TSG101 interaction with HRS mediates endosomal trafficking and receptor down-regulation. findings: [] - id: PMID:12900395 title: Hrs regulates multivesicular body formation via ESCRT recruitment to endosomes. findings: [] - id: PMID:14505570 title: The protein network of HIV budding. findings: [] - id: PMID:14519844 title: Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins. findings: [] - id: PMID:15033475 title: Physical and functional interactions between Daxx and TSG101. findings: [] - id: PMID:15126635 title: Nedd4.1-mediated ubiquitination and subsequent recruitment of Tsg101 ensure HTLV-1 Gag trafficking towards the multivesicular body pathway prior to virus budding. findings: [] - id: PMID:15218037 title: The human endosomal sorting complex required for transport (ESCRT-I) and its role in HIV-1 budding. findings: [] - id: PMID:15326289 title: Identification and proteomic profiling of exosomes in human urine. findings: [] - id: PMID:15611048 title: Interactions of TOM1L1 with the multivesicular body sorting machinery. findings: [] - id: PMID:16118794 title: 'SIMPLE interacts with NEDD4 and TSG101: evidence for a role in lysosomal sorting and implications for Charcot-Marie-Tooth disease.' findings: [] - id: PMID:16189514 title: Towards a proteome-scale map of the human protein-protein interaction network. findings: [] - id: PMID:16501490 title: Collection, storage, preservation, and normalization of human urinary exosomes for biomarker discovery. findings: [] - id: PMID:16554368 title: The ESCRT-III subunit hVps24 is required for degradation but not silencing of the epidermal growth factor receptor. findings: [] - id: PMID:16973552 title: Human ESCRT-II complex and its role in human immunodeficiency virus type 1 release. findings: [] - id: PMID:17174262 title: HD-PTP and Alix share some membrane-traffic related proteins that interact with their Bro1 domains or proline-rich regions. findings: [] - id: PMID:17229889 title: Spongiform neurodegeneration-associated E3 ligase Mahogunin ubiquitylates TSG101 and regulates endosomal trafficking. findings: [] - id: PMID:17350572 title: Structural and biochemical studies of ALIX/AIP1 and its role in retrovirus budding. findings: [] - id: PMID:17714434 title: Vps22/EAP30 in ESCRT-II mediates endosomal sorting of growth factor and chemokine receptors destined for lysosomal degradation. findings: [] - id: PMID:17853893 title: Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis. findings: [] - id: PMID:17940959 title: Involvement of vacuolar protein sorting pathway in Ebola virus release independent of TSG101 interaction. findings: [] - id: PMID:18005716 title: Identification of human MVB12 proteins as ESCRT-I subunits that function in HIV budding. findings: [] - id: PMID:18077552 title: 'Regulation of Tsg101 expression by the steadiness box: a role of Tsg101-associated ligase.' findings: [] - id: PMID:18256029 title: 'Identification of Alix-type and Non-Alix-type ALG-2-binding sites in human phospholipid scramblase 3: differential binding to an alternatively spliced isoform and amino acid-substituted mutants.' findings: [] - id: PMID:18641129 title: Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release. findings: [] - id: PMID:19056867 title: Large-scale proteomics and phosphoproteomics of urinary exosomes. findings: [] - id: PMID:19060904 title: An empirical framework for binary interactome mapping. findings: [] - id: PMID:19520058 title: Penta-EF-hand protein ALG-2 functions as a Ca2+-dependent adaptor that bridges Alix and TSG101. findings: [] - id: PMID:19549727 title: Analysis of the human E2 ubiquitin conjugating enzyme protein interaction network. findings: [] - id: PMID:20176808 title: TEX14 interacts with CEP55 to block cell abscission. findings: [] - id: PMID:20588296 title: 'Membrane budding and scission by the ESCRT machinery: it''s all in the neck.' findings: [] - id: PMID:20654576 title: Distinct functions of human MVB12A and MVB12B in the ESCRT-I dependent on their posttranslational modifications. findings: [] - id: PMID:21118109 title: The role of ESCRT proteins in fusion events involving lysosomes, endosomes and autophagosomes. findings: [] - id: PMID:21757351 title: UBAP1 is a component of an endosome-specific ESCRT-I complex that is essential for MVB sorting. findings: [] - id: PMID:22232651 title: Structural basis for membrane targeting by the MVB12-associated β-prism domain of the human ESCRT-I MVB12 subunit. findings: [] - id: PMID:22315426 title: Formation and release of arrestin domain-containing protein 1-mediated microvesicles (ARMMs) at plasma membrane by recruitment of TSG101 protein. findings: [] - id: PMID:22660413 title: Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. findings: [] - id: PMID:23092844 title: Monitoring the Rab27 associated exosome pathway using nanoparticle tracking analysis. findings: [] - id: PMID:23166352 title: Charcot-Marie-Tooth disease-linked protein SIMPLE functions with the ESCRT machinery in endosomal trafficking. findings: [] - id: PMID:23533145 title: In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. findings: [] - id: PMID:24105262 title: Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. findings: [] - id: PMID:25416956 title: A proteome-scale map of the human interactome network. findings: [] - id: PMID:26871637 title: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. findings: [] - id: PMID:27107012 title: Pooled-matrix protein interaction screens using Barcode Fusion Genetics. findings: [] - id: PMID:28514442 title: Architecture of the human interactome defines protein communities and disease networks. findings: [] - id: PMID:31515488 title: Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. findings: [] - id: PMID:32296183 title: A reference map of the human binary protein interactome. findings: [] - id: PMID:32424346 title: A helical assembly of human ESCRT-I scaffolds reverse-topology membrane scission. findings: [] - id: PMID:33961781 title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. findings: [] - id: PMID:35044719 title: Proteome-scale mapping of binding sites in the unstructured regions of the human proteome. findings: [] - id: PMID:35271311 title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.' findings: [] - id: PMID:37100772 title: Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs. findings: [] - id: PMID:37219487 title: Large-scale phosphomimetic screening identifies phospho-modulated motif-based protein interactions. findings: [] - id: PMID:39526800 title: A comprehensive two-hybrid analysis to explore the Legionella pneumophila effector-effector interactome. findings: [] - id: PMID:40205054 title: Multimodal cell maps as a foundation for structural and functional genomics. findings: [] - id: PMID:9241264 title: TSG101 may be the prototype of a class of dominant negative ubiquitin regulators. findings: [] - id: Reactome:R-HSA-184269 title: Monoubiquitinated N-myristoyl GAG polyprotein is targeted to the late endosomal vesicle membrane by the ESCRT-I complex findings: [] - id: Reactome:R-HSA-3149434 title: Transport of GAG to the Plasma Membrane findings: [] - id: Reactome:R-HSA-3159232 title: Recruitment Of HIV Virion Budding Machinery findings: [] - id: Reactome:R-HSA-917696 title: Cargo Sequestration findings: [] - id: Reactome:R-HSA-917730 title: Cargo Recognition And Sorting findings: [] - id: PMID:31010855 title: Rab5-dependent autophagosome closure by ESCRT. findings: [] - id: PMID:31519728 title: VPS37A directs ESCRT recruitment for phagophore closure. findings: [] - id: file:human/TSG101/TSG101-uniprot.txt title: UniProtKB record for human TSG101 findings: [] - id: file:human/TSG101/TSG101-notes.md title: TSG101 review notes findings: [] core_functions: - molecular_function: id: GO:0043130 label: ubiquitin binding description: TSG101 is the UEV-domain ESCRT-I adaptor/scaffold that binds ubiquitin/PTAP-type motifs and organizes ESCRT-I for ubiquitinated endocytic cargo sorting, MVB membrane remodeling, and ESCRT-dependent phagophore/autophagosome closure. directly_involved_in: - id: GO:0043162 label: ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway - id: GO:0036258 label: multivesicular body assembly - id: GO:0090148 label: membrane fission - id: GO:0000045 label: autophagosome assembly locations: - id: GO:0010008 label: endosome membrane - id: GO:0031901 label: early endosome membrane - id: GO:0031902 label: late endosome membrane in_complex: id: GO:0000813 label: ESCRT I complex supported_by: - *id006 - *id007 - *id008 - *id009 - *id010 - *id011 - *id012 - *id013 - *id022 - *id023 - *id024 - *id025 - *id026 - *id027 - *id028 - *id029 - *id030 - *id031 - *id032 - *id033 - *id034 proposed_new_terms: [] suggested_questions: - question: Should the TSG101 autophagy annotation be changed from broad macroautophagy/autophagosome maturation to GO:0000045 autophagosome assembly for phagophore closure? experts: - GO autophagy editors - GO ESCRT curators - question: Should generic TSG101 protein-binding annotations be retired in favor of ubiquitin binding, ESCRT-I complex membership, and specific pathway contexts? experts: - GO molecular function editors - UniProt curators - question: Should viral budding, cytokinesis, and exosome annotations remain non-core branches in proteostasis-focused TSG101 curation? experts: - GO viral process editors - GO cell-cycle editors - GO extracellular vesicle editors suggested_experiments: - experiment_type: TSG101 separation-of-function phagophore closure rescue hypothesis: TSG101 UEV-domain ubiquitin/PTAP-motif binding and ESCRT-I assembly surfaces make separable contributions to phagophore closure and MVB cargo sorting. description: Use acute TSG101 depletion/rescue with UEV-domain and VPS28/VPS37-binding mutants, then measure HT-LC3 closure, EGFR MVB sorting, and ESCRT-III/VPS4 recruitment side by side. - experiment_type: endogenous ESCRT-I autophagy recruitment imaging hypothesis: Core ESCRT-I components including TSG101 transiently localize to closing LC3-positive phagophores before ESCRT-III/VPS4 recruitment. description: Endogenously tag TSG101, VPS28, VPS37A, CHMP2A, and LC3 reporters and quantify recruitment order during starvation-induced phagophore closure.